Tetrapeptide effect on experimental diabetes mellitus

The analysis of amino acid sequences of insulinotropic polypeptides has revealed a common short segment, consisting of four amino acid residues. Tetrapeptide KEDWa, analogous to this segment and protected from the effects of amino acid proteinases, has been synthesized. Intramuscular administration of this tetrapeptide for 11 days to rats with alloxan diabetes partially restored the insulin synthesis. The degree of inclination of the sugar curve in this case was similar to that of healthy animals. Oral or intramuscular administration of the tetrapeptide for 10 days to rats with experimental streptosotocin diabetes showed, that orally administered tetrapeptide exerted a pronounced hypoglycaemic effect during its administration. Intramuscular administration normalized the adhesive ability of mesentery microvesseis endothelium, at the same time not affecting their permeability These results point out a hypoglycaemic and endothelioprotective effect of the tetrapeptide in case of experimental diabetes mellitus. It was suggested, that the tetrapeptide is an activator of promoter segment of preproinsulin gene, and that it complementarily interacts with nucleotide sequences ggcagg and cctgcc ofthe leading strand of the DNA double helix.